Abstract

Background: Iron is an essential mineral for both cellular and pathogen survival and is essential for viral replication. In turn, iron metabolism has been shown to be altered by several viral infections. However, little is known regarding the association between iron status and HPV natural history. We hypothesize iron to be an HPV-cofactor that is associated with longer duration of infection.
Methods: Ferritin and soluble transferrin receptor (sTfR) were measured in baseline serum samples from 327 women enrolled in the Ludwig-McGill Cohort. Incident HPV clearance rates (any-type, oncogenic HPV, non-oncogenic HPV, and HPV-16) over 36 months were estimated from Cox-proportional hazard models accounting for correlations between multiple infections.
Results: Women with ferritin levels above the median were less likely to clear an incident oncogenic HPV (AHR=0.73; 95%CI 0.55-0.96) and HPV-16 infections (AHR=0.29; 95%CI 0.11-0.73). Using physiological cut-points, women with enriched iron stores (>120μg/L) were less likely to clear incident oncogenic HPV infections compared to those with low-levels of iron (<20μg/L)( AHR=0.34; 95%CI 0.15-0.81).
Conclusion: This study observed that women with the highest ferritin levels were less likely to clear incident oncogenic and HPV-16 infections compared to women with low ferritin. Rising iron stores may decrease probability of clearing new HPV infection, possibly by promoting viral activity and contributing to oxidative DNA damage.
Impact: This novel study suggests that elevated iron stores may put women at risk for persistent HPV infection, an early event in cervical carcinogenesis. Further examination of the association between iron status and HPV natural history is warranted.